Q1LZ53 (DNM3A_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA (cytosine-5)-methyltransferase 3A
Short name=Dnmt3a
EC=2.1.1.37

Gene names

Name:

Dnmt3a

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	908 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNA methylation is coordinated with methylation of histones. It modifies DNA in a non-processive manner and also methylates non-CpG sites. May preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1. Plays a role in paternal and maternal imprinting. Required for methylation of most imprinted loci in germ cells. Acts as a transcriptional corepressor for ZBTB18. Can actively repress transcription through the recruitment of HDAC activity By similarity.
Catalytic activity	S-adenosyl-L-methionine + DNA = S-adenosyl-L-homocysteine + DNA containing 5-methylcytosine.
Enzyme regulation	Activated by binding to the regulatory factor DNMT3L By similarity.
Subunit structure	Heterotetramer composed of 1 DNMT3A homodimer and 2 DNMT3L subunits (DNMT3L-DNMT3A-DNMT3A-DNMT3L) By similarity. Interacts with DNMT1 and DNMT3B. Binds the ZBTB18 transcriptional repressor. Interacts with SETDB1. Associates with HDAC1 through its ADD domain By similarity. Interacts with the PRC2/EED-EZH2 complex By similarity. Interacts with UBC9, PIAS1 and PIAS2 By similarity. Interacts with MPHOSPH8. Interacts with histone H3 that is not methylated at 'Lys-4' (H3K4). Interacts with UHRF1 By similarity.
Subcellular location	Nucleus By similarity. Cytoplasm By similarity.
Domain	The PWWP domain is essential for targeting to pericentric heterochromatin.
Post-translational modification	Sumoylated; sumoylation disrupts the ability to interact with histone deacetylases (HDAC1 and HDAC2) and repress transcription By similarity.
Sequence similarities	Belongs to the C5-methyltransferase family. Contains 1 ADD domain. Contains 1 GATA-type zinc finger. Contains 1 PHD-type zinc finger. Contains 1 PWWP domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative promoter usage
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding S-adenosyl-L-methionine Zinc
Molecular function	Chromatin regulator Methyltransferase Repressor Transferase
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA methylation involved in embryo development Inferred from electronic annotation. Source: Compara DNA methylation involved in gamete generation Inferred from electronic annotation. Source: Compara DNA methylation on cytosine within a CG sequence Inferred from direct assay PubMed 11844796. Source: RGD S-adenosylhomocysteine metabolic process Inferred from direct assay PubMed 11844796. Source: RGD S-adenosylmethioninamine metabolic process Inferred from direct assay PubMed 11844796. Source: RGD cellular response to amino acid stimulus Inferred from electronic annotation. Source: Compara hypermethylation of CpG island Inferred from electronic annotation. Source: Compara methylation-dependent chromatin silencing Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara regulation of gene expression by genetic imprinting Inferred from electronic annotation. Source: Compara spermatogenesis Inferred from electronic annotation. Source: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	chromosome, centromeric region Inferred from electronic annotation. Source: Compara cytoplasm Inferred from sequence or structural similarity PubMed 12138111. Source: UniProtKB euchromatin Inferred from sequence or structural similarity PubMed 12138111. Source: UniProtKB nuclear heterochromatin Inferred from electronic annotation. Source: Compara nuclear matrix Inferred from sequence or structural similarity PubMed 12138111. Source: UniProtKB
Molecular_function	DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates Inferred from direct assay PubMed 11844796. Source: RGD chromatin binding Inferred from electronic annotation. Source: Compara metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW unmethylated CpG binding Inferred from direct assay PubMed 11844796. Source: RGD
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative promoter usage. [Align] [Select]

Isoform 1 (identifier: Q1LZ53-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q1LZ53-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-219: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 908	908	DNA (cytosine-5)-methyltransferase 3A		PRO_0000313030
Regions
	Domain	257 – 315	59	PWWP
	Domain	478 – 610	133	ADD
	Zinc finger	489 – 519	31	GATA-type; atypical
	Zinc finger	530 – 586	57	PHD-type; atypical
	Region	195 – 399	205	Interaction with DNMT1 and DNMT3B By similarity
	Region	490 – 582	93	Interaction with the PRC2/EED-EZH2 complex By similarity
	Region	637 – 641	5	S-adenosyl-L-methionine binding By similarity
	Region	682 – 684	3	S-adenosyl-L-methionine binding By similarity
	Region	887 – 889	3	S-adenosyl-L-methionine binding By similarity
	Compositional bias	479 – 527	49	Cys-rich
Sites
	Active site	706	1	By similarity
	Binding site	660	1	S-adenosyl-L-methionine By similarity
Amino acid modifications
	Modified residue	102	1	Phosphoserine By similarity
	Modified residue	239	1	Phosphoserine By similarity
	Modified residue	251	1	Phosphoserine By similarity
	Modified residue	257	1	Phosphothreonine By similarity
Natural variations
	Alternative sequence	1 – 219	219	Missing in isoform 2.		VSP_029986

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 30, 2006. Version 1. Checksum: 6CCE9EB4E9CEB409	FASTA	908	101,669
	10 20 30 40 50 60 MPSSGPGDTS ISSLEREDDR KEGEEQEENR GKEERQEPSA TARKVGRPGR KRKHPPVESS 70 80 90 100 110 120 DTPKDPAVTT KSQPTAQDSG PSDLLPNGDL EKRSEPQPEE GSPAAGQKGG APAEGEGTET 130 140 150 160 170 180 PPEASRAVEN GCCVTKEGRG ASAGEGKEQK QTNIESMKME GSRGRLRGGL GWESSLRQRP 190 200 210 220 230 240 MPRLTFQAGD PYYISKRKRD EWLARWKREA EKKAKVIAVM NAVEESQASG ESQKVEEASP 250 260 270 280 290 300 PAVQQPTDPA SPTVATTPEP VGADAGDKNA TKAADDEPEY EDGRGFGIGE LVWGKLRGFS 310 320 330 340 350 360 WWPGRIVSWW MTGRSRAAEG TRWVMWFGDG KFSVVCVEKL MPLSSFCSAF HQATYNKQPM 370 380 390 400 410 420 YRKAIYEVLQ VASSRAGKLF PACHDSDESD TGKAVEVQNK QMIEWALGGF QPSGPKGLEP 430 440 450 460 470 480 PEEEKNPYKE VYTDMWVEPE AAAYAPPPPA KKPRKSTTEK PKVKEIIDER TRERLVYEVR 490 500 510 520 530 540 QKCRNIEDIC ISCGSLNVTL EHPLFIGGMC QNCKNCFLEC AYQYDDDGYQ SYCTICCGGR 550 560 570 580 590 600 EVLMCGNNNC CRCFCVECVD LLVGPGAAQA AIKEDPWNCY MCGHKGTYGL LRRREDWPSR 610 620 630 640 650 660 LQMFFANNHD QEFDPPKVYP PVPAEKRKPI RVLSLFDGIA TGLLVLKDLG IQVDRYIASE 670 680 690 700 710 720 VCEDSITVGM VRHQGKIMYV GDVRSVTQKH IQEWGPFDLV IGGSPCNDLS IVNPARKGLY 730 740 750 760 770 780 EGTGRLFFEF YRLLHDARPK EGDDRPFFWL FENVVAMGVS DKRDISRFLE SNPVMIDAKE 790 800 810 820 830 840 VSAAHRARYF WGNLPGMNRP LASTVNDKLE LQECLEHGRI AKFSKVRTIT TRSNSIKQGK 850 860 870 880 890 900 DQHFPVFMNE KEDILWCTEM ERVFGFPVHY TDVSNMSRLA RQRLLGRSWS VPVIRHLFAP LKEYFACV
	Isoform 2 [UniParc]. Checksum: 1C75674CFC1C97BE	FASTA	689	77,825
	10 20 30 40 50 60 MNAVEESQAS GESQKVEEAS PPAVQQPTDP ASPTVATTPE PVGADAGDKN ATKAADDEPE 70 80 90 100 110 120 YEDGRGFGIG ELVWGKLRGF SWWPGRIVSW WMTGRSRAAE GTRWVMWFGD GKFSVVCVEK 130 140 150 160 170 180 LMPLSSFCSA FHQATYNKQP MYRKAIYEVL QVASSRAGKL FPACHDSDES DTGKAVEVQN 190 200 210 220 230 240 KQMIEWALGG FQPSGPKGLE PPEEEKNPYK EVYTDMWVEP EAAAYAPPPP AKKPRKSTTE 250 260 270 280 290 300 KPKVKEIIDE RTRERLVYEV RQKCRNIEDI CISCGSLNVT LEHPLFIGGM CQNCKNCFLE 310 320 330 340 350 360 CAYQYDDDGY QSYCTICCGG REVLMCGNNN CCRCFCVECV DLLVGPGAAQ AAIKEDPWNC 370 380 390 400 410 420 YMCGHKGTYG LLRRREDWPS RLQMFFANNH DQEFDPPKVY PPVPAEKRKP IRVLSLFDGI 430 440 450 460 470 480 ATGLLVLKDL GIQVDRYIAS EVCEDSITVG MVRHQGKIMY VGDVRSVTQK HIQEWGPFDL 490 500 510 520 530 540 VIGGSPCNDL SIVNPARKGL YEGTGRLFFE FYRLLHDARP KEGDDRPFFW LFENVVAMGV 550 560 570 580 590 600 SDKRDISRFL ESNPVMIDAK EVSAAHRARY FWGNLPGMNR PLASTVNDKL ELQECLEHGR 610 620 630 640 650 660 IAKFSKVRTI TTRSNSIKQG KDQHFPVFMN EKEDILWCTE MERVFGFPVH YTDVSNMSRL 670 680 ARQRLLGRSW SVPVIRHLFA PLKEYFACV

References

[1]	"Identification of 11 pseudogenes in the DNA methyltransferase gene family in rodents and humans and implications for the functional loci." Lees-Murdock D.J., McLoughlin G.A., McDaid J.R., Quinn L.M., O'Doherty A., Hiripi L., Hack C.J., Walsh C.P. Genomics 84:193-204(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	BN000395 mRNA. Translation: CAE52317.1. BN000396 mRNA. Translation: CAE52318.1.
IPI	IPI00387877. IPI00760141.
RefSeq	NP_001003957.1. NM_001003957.1. NP_001003958.1. NM_001003958.1.
UniGene	Rn.92659.
3D structure databases
ProteinModelPortal	Q1LZ53.
SMR	Q1LZ53. Positions 279-420, 623-908.
ModBase	Search...
PTM databases
PhosphoSite	Q1LZ53.
Proteomic databases
PaxDb	Q1LZ53.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000047210; ENSRNOP00000046524; ENSRNOG00000026649.
GeneID	444984.
KEGG	rno:444984.
Organism-specific databases
CTD	1788.
RGD	1303336. Dnmt3a.
Phylogenomic databases
eggNOG	NOG70699.
GeneTree	ENSGT00390000008341.
HOGENOM	HOG000230875.
HOVERGEN	HBG051381.
InParanoid	Q1LZ53.
KO	K00558.
OrthoDB	EOG4T1HKX.
Gene expression databases
ArrayExpress	Q1LZ53.
Genevestigator	Q1LZ53.
Family and domain databases
InterPro	IPR025766. ADD. IPR018117. C5_DNA_meth_AS. IPR001525. C5_MeTfrase. IPR025811. C5_MeTrfase_3. IPR000313. PWWP. IPR011011. Znf_FYVE_PHD. [Graphical view]
Pfam	PF00145. DNA_methylase. 1 hit. PF00855. PWWP. 1 hit. [Graphical view]
SMART	SM00293. PWWP. 1 hit. [Graphical view]
SUPFAM	SSF57903. FYVE_PHD_ZnF. 1 hit.
PROSITE	PS51533. ADD. 1 hit. PS00094. C5_MTASE_1. 1 hit. PS00095. C5_MTASE_2. False negative. PS50812. PWWP. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	697058.

Entry information

Entry name

DNM3A_RAT

Accession

Primary (citable) accession number: Q1LZ53
Secondary accession number(s): Q1LZ52

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 15, 2008
Last sequence update:	May 30, 2006
Last modified:	May 1, 2013
This is version 60 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program